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Biomedical subjects

D Naor

Publications and source records attributed to D Naor.

At least 91 records · Page 5Linked to original sources
PubMed1978

Immune responses to weakly immunogenic virally induced tumors. I. Overcoming low responsiveness by priming mice with a syngeneic in vitro tumor line or allogeneic cross-reactive tumor.

This report describes model systems which show low primary in vitro syngeneic cytotoxic responses to a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBL5 tumor (syngeneic in C57BL/6 mice) and examines different approaches to overcome these defects. Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed to generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the cross-reactive allogeneic tumor RBL5, could generate significant cytotoxic responses to the syngeneic tumors YAC and YAC-1. Similarly, spleen cells from C57BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response to the syngeneic tumor RBL5. Thus, cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.

Animals↗
PubMed1978

Immune responses to weakly immunogenic virally induced tumors. II. Suppressive effects of the in vivo carried tumor YAC.

Unprimed spleen cells from A and C57BL/6 mice could not produce cytotoxic responses to their syngeneic tumors: a Moloney virus-induced in vitro subline YAC-1 and a Rauscher virus-induced in vitro subline RBL5, respectively. Spleen cells from A and C57BL/6 mice immunized with YAC-1 OR RBL5 (which cross-react serologically) generated significant syngeneic cytotoxicities after cultivation in vitro. The in vivo carried tumor of A mice, unlike the in vitro sublines, could not stimulate a priming effect. In contrast, YAC stimulated the formation of suppressor cells in both A and C57BL/6 mice. The suppressor cells abrogated the priming effect of the syngeneic tumors, but not the priming effect of the allogeneic tumors. Furthermore, YAC did not suppress normal allogeneic anti-tumor responses. The theoretical and the practical implications of these studies are discussed.

Animals↗
PubMed1978

Cellular assay for measuring anti-erythrocyte antibody responses.

Splenocytes from mice immunized with sheep red cells (SRC) or donkey red cells (DRC) were able to lyse radiolabeled SRC or DRC respectively. The cytotoxic effect was mediated by the active supernatant which was released from the immune splenocytes and which was characterized as antibody. This cellular cytotoxic response was found to be a very reliable, efficient, rapid and objective assay for measuring anti-erythrocyte antibody responses.

Animals↗
PubMed1978

Studies on the immune response to fixed antigens. III. Induction of helper function for antibody-dependent cellular cytotoxicity responses.

Heavy trinitrophenylated sheep red cells (TNP128SRC) and glutaraldehyde-treated SRC (G-SRC) could not induce cellular cytotoxicity against 51Cr-SRC. In contrast, the native antigen SRC could stimulate a cytolytic response against the radiolabeled homologous target cell. However, fixed SRC could stimulate a priming function that accelerated and augmented the secondary cytotoxic response to SRC. Such fixed antigens could stimulate a delayed-type hypersensitivity (DTHS) response also. Thus, the immunologic memory to the chemically modified antigen, as well as the DTHS response, are completely dissociated from the primary cytotoxic responses. The primary and the secondary cytotoxic responses that were developed in the spleens of the injected mice were mediated by antibody-dependent cellular cytotoxicity (ADCC), since the active supernatant that was released from the spleen cells could lyse the target cells in the presence of normal splenocytes. The active supernatant was identified as antibody. We suggest that B effector cells cytolyzed the antibody-coated target cells. Normal cells from nude mice could mediate the cytolytic process as efficiently as spleen cells from other strains of mouse. The results are discussed in terms of selective stimulation of T cell subpopulations.

Absorption↗
PubMed1977

Cryopreservation of immunological memory and other lymphoid cell functions.

The following components of the immune response by mouse spleen cells were retained after cryopreservation at --110 degrees C: direct and indirect plaque formation, avidity of antibody secreted by plaque forming cells, and induction of primary or secondary adoptive transfer responses. Human peripheral blood lymphocytes retained the capacity to mediate antibody-dependent cytotoxicity and cell mediated immunity to tumor in vitro.

Animals↗
PubMed1977

Studies on the immune response to fixed antigens. II. Optimal conditions for inducing and eliciting helper function by fixed antigens and the mechanism responsible for this effect.

Heavily trinitrophenylated sheep red blood cells (RBC) (TNP128SRBC) and glutaraldehyde-treated SRBC (G-SRBC) induced helper function. This helper function could accelerate anti-SRBC and anti-TNP secondary responses to subsequent challenge with TNP0.14SRBC in different strains of mouse. Preferential induction of helper function over primary antibody response was obtained with fixed antigens only. High doses of fixed RBC (4 X 10(7) or 4 x 10(8)/mouse) could induce optimal helper function and high doses of the challenger TNP0.14SRBC (4 X 10(7) or 4 x 10(8)/mouse) could optimally recall this function and stimulate secondary responses. G-SRBC was a better inducer of helper function than low doses of nonmodified SRBC. TNP128SRBC-primed mice produced a significant anti-SRBC response after subsequent challenge with TNP0.14 mouse RBC. Reverse help was suggested as one of the possible mechanisms of this response. Early helper function which developed four days after priming with TNP128SRBC or G-SRBC could be transferred to irradiated recipients with T, but not B, cells. Late immunologic memory which appeared 18 days after priming with TNP128SRBC could be transferred to irradiated recipients only with a mixture of T and B cells.

Animals↗
PubMed1976

Induction of immune responsiveness in a genetically low-responsive tumor-host combination by chemical modification of the immunogen.

Trinitrophenylated Moloney virus-induced YAC cells induced a higher cytotoxic antibody response and better protection against small tumor cell doses in syngeneic, low-responsive strain A mice than nonmodified YAC cells that had been inactivated by irradiation or mitomycin C treatment. The results indicated that genetically determined low responsiveness to a virally induced antigen can be overcome, at least to some extent, by coupling the immunizing cells to a strong immunogenic hapten.

Animals↗
PubMed1976

Immune response of New Zealand mice to trinitrophenylated syngeneic mouse red cells.

NZB and NZB/W mice have reduced anti-sheep red cell (SRC) and 2,4,6-trinitrophenyl-plaque-froming cell (TNP-PFC) responses with age after injection of either the thymus-dependent antigen TNP-SRC or the thymus-independent antigen TNP-mouse red cells (MRC). However, the thymus-dependent response diminished much faster than the thymus-independent response. As a consequence, young New Zealand mice have a higher anti-TNP response after injection of TNP-SRC than after injection of TNP-MRC, while old New Zealand mice have a higher anti-TNP response after injection of TNP-MRC than after injection of TNP-SRC. The PFC avidity of NZB/W mice injected with TNP-SRC diminished with age, while the PFC avidity of mice injected with TNP-MRC did not change with agrc or TNP-SRC. Old NZB/W mice had few spontaneous anti-MRC-PFC. The number of anti-MRC PFC in old mice was increased 4 to 10 times after injection with either TNP-SRC or TNP-MRC. It is suggested that surveillance mechanisms are responsible for suppressing the autoimmune response to modified self-antigens. The unregulated immune system of NZB and NZB/W mice appears to be an expression of impairment of such a hypothetical surveillance mechanism.

Age Factors↗
PubMed1976

Immunogenicity of tumor cells modified by trinitrobenzene suflonic acid (TNBS).

The ability of trinitrophenylated tumor cells to stimulate syngeneic antitumor response has been tested in 3 different tumor-host systems: A. Trinitrophenylated and inactivated Moloney induced YAC tumor cells (YAC-TNP) were able to induce the production of cytotoxic antibodies in low responding A/J mice, while inactivated YAC tumor cells (YAC-In) failed to induce such a response. Furthermore, A mice which were injected with YAC-TNP rejected 103 viable YAC tumor cells at a higher frequency than those injected with YAC-In. B. Trinitrophenylated and inactivated Gross virus induced G-35 tumor cells or Monoloney induced LSTRA cells (both syngeneic in BALB/c mice) were as immunogenic as nonmodified inactivated tumor cells. About 50% of the immunized mice survived indefinitely after injection of 103 viable tumors. Fruthermore, spleen cells from mice primed with either modified or nonomodified G-35 cells responded in vitro to G-35 in a mixed leukocyte tumor interaction and generated specific cell-mediated cytotoxic activity to 51Cr-G-35 syngeneic tumors. However, the donors of the primed cells did not produce detectable cytotoxic antibodies to G-35. C. In vitro sensitization of C57B1 spleen cells by trinitrophenylated Mitomycin C treated syngeneic EL-4 generated a stronger cytotoxic response to EL-4 cells than obtained by sensitization with Mitomycin C treated EL-4 cells alone, The superiority of the sensitizing capacity of trinitrophenylated EL-4 was readily demonstrated in conditions which were suboptimal for nonmodified Mitomycin C treated tumor. Both theoretical and practical implications of these results are discussed.

Animals↗
PubMed1976

Autoimmunity and aging: the age-related response of mice of a long-lived strain to trinitrophenylated syngeneic mouse red blood cells.

Mice of 1.5, 9, 22, and 31 to 32 months of age were injected with the thymus-dependent antigen, TNP-SRC, or the thymus-independent antigen, TNP-SRC, TNP-MRC. The anti-SRC and TNP immune responses to TNP-SRC were markedly reduced in older mice, whereas the anti-TNP response to the TNP-MRC showed no substantial decline. Young mice produced higher anti-TNP plaque-forming cell responses after injection of TNP-SRC than after TNP-MRC, whereas in older mice the reverse obtained. Old mice but not young mice displayed a high anti-SRC cross-reactive response after injection of TNP-MRC. The avidity of anti-TNP antibody of young mice immunized with TNP-SRC was higher than that following immunization with TNP-MRC, whereas the avidities of anti-TNP antibodies from old mice injected with these two reagents were the same. Those individual mice which showed a poorly regulated immune response also displayed an autologous anti-MRC plaque-forming cell response after injection of either TNP-SRC or TNP-MRC. It is suggested that mechanisms mediated by suppressor T cells may be responsible for regulating the autoimmune response to modified self antigens, and that these are severely impaired in age individuals.

Aging↗
PubMed1976

Studies on the immune response to fixed antigens. Preferential induction of helper function with heavily trinitrophenylated sheep erythrocytes, and glutaraldehyde-treated sheep erythrocytes.

Mice primed with heavily trinitrophenylated sheep red cells (TNP128SRC) or glutaraldehyde-treated sheep red cells (G-SRC) developed an early helper function mediated by thymus-derived cells. Such mice were able to produce high secondary responses to both hapten and carrier after challenge 2 days after priming, with lightly trinitrophenylated SRC (TNP0.14SRC). However, the primary response of the TNP128SRC or G-SRC-primed mice were very low to undetectable, and their secondary responses were also low when the challenge antigen was administered 4 days after priming or later. Inhibitory humoral factor(s) which were induced in the primed animals appeared responsible for the decreased capacity of primed mice to mount a secondary response when challenged later than 2 days after priming. Transfer of spleen cells from TNP128SRC-primed mice to sublethally irradiated recipients circumvents their exposure to inhibitory humoral factor(s) present in intact animals allowing them to react with challenge antigen. Enriched populations of T cells, but not B cells, were able to transfer this early immunologic memory to irradiated recipients. The theoretical and practical implications of these results are discussed.

Aldehydes↗
PubMed1975

Lack of requirement for thymocytes for efficient antibody formation to trinitrophenylated mouse red cells in mice: role for thymocytes in suppression of the immune response.

The requirement of thymus-derived cells for the immune response to trinitrophenylated syngeneic mouse red cells (TNP-MRC) was investigated. In three sets of experiments the following results were obtained: a) irradiated mice which were reconstituted with bone marrow cells alone showed a better anti-TNP response after injection with TNP-MRC than those reconstituted with both bone marrow cells and thymocytes. b) Anti-thymocyte serum augmented the mouse anti-TNP response to TNP-MRC. c) Nude thymusless mice showed a better anti-TNP response to TNP-MRC than their normal littermate controls. These results indicate that the anti-TNP response of mice to TNP-MRC does not require thymus-derived helper cells. Moreover, thymus-derived cells have a suppressive effect on the anti-TNP response.

Animals↗
PubMed1974

Restoration of immune competence in tolerant mice by parabiosis to normal mice.

These studies demonstrate that mice tolerant to human gamma globulin (HGG) regain their ability to make antibody to HGG after parabiosis to normal mice. This can be demonstrated by enumeration of PFC in the spleens of both the normal and tolerant partners. Hemagglutinin titers of normal-tolerant parabionts, however, are exceptionally low; serum antibody appears to be neutralized by circulating HGG present originally in the serum of the tolerant partner. These data support the hypothesis that tolerance to HGG in mice is a "defective" state due to the absence of cells capable of responding to this antigen.

Animals↗